{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:02:23Z","timestamp":1791414143375,"version":"4.3.3"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Ceftazidime-avibactam is a \u03b2-lactam \u03b2-lactamase inhibitor combination under investigation for the treatment of serious Gram-negative infections. When combined with avibactam, a novel non-\u03b2-lactam \u03b2-lactamase inhibitor, ceftazidime has activity against isolates that produce Ambler class A, class C, and some class D \u03b2-lactamases. However, little is known of the\n in vivo<\/jats:italic>\n efficacy of the combination against these targeted ceftazidime- and carbapenem-resistant\n Enterobacteriaceae<\/jats:named-content>\n . Using humanized exposures in the murine thigh model, we evaluated the efficacy of ceftazidime-avibactam against\n Enterobacteriaceae<\/jats:named-content>\n exhibiting MICs of \u22658 \u03bcg\/ml to aid in the assignment of interpretive susceptibility criteria. Eighteen clinical\n Enterobacteriaceae<\/jats:named-content>\n isolates, including nine carbapenem-resistant strains, were evaluated against ceftazidime-avibactam (2,000 mg\/500 mg) as a 2-h infusion every 8 h. To highlight the impact of avibactam, 13 select isolates were tested in the neutropenic model against a humanized regimen of 2,000 mg ceftazidime every 8 h (2-h infusion). Additionally, nine isolates were evaluated in immunocompetent animals. The efficacy was evaluated as the change in log\n 10<\/jats:sub>\n CFU compared with that of 0-h controls after 24 h. The vast majority (17\/18, 94%) of the isolates were resistant to ceftazidime alone. The ceftazidime monotherapy failed to have activity against 10 of 13 isolates, while ceftazidime-avibactam produced reductions in bacterial density against 16 of 18 isolates. Ceftazidime-avibactam (2,000 mg\/500 mg) every 8 h (2-h infusion) displayed dependable activity against the\n Enterobacteriaceae<\/jats:named-content>\n isolates, exhibiting MICs of \u226416 \u03bcg\/ml (free drug concentration above the MIC [\n f<\/jats:italic>\n T\n >MIC<\/jats:sub>\n ] of \u226562%) and variable activity was noted at an MIC of 32 \u03bcg\/ml (\n f<\/jats:italic>\n T\n >MIC<\/jats:sub>\n of 34%). The presence of a functioning immune system enhanced the efficacy for both regimens against all tested isolates. These data support further examination of the use of ceftazidime-avibactam as an effective therapy against infections due to Gram-negative infections, including carbapenem-resistant\n Enterobacteriaceae<\/jats:named-content>\n .\n <\/jats:p>","DOI":"10.1128\/aac.03267-14","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T08:27:40Z","timestamp":1410856060000},"page":"6913-6919","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["In Vivo<\/i>\n Efficacy of Humanized Exposures of Ceftazidime-Avibactam in Comparison with Ceftazidime against Contemporary Enterobacteriaceae Isolates"],"prefix":"10.1128","volume":"58","author":[{"given":"Shawn H.","family":"MacVane","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared L.","family":"Crandon","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wright W.","family":"Nichols","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals LP, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"},{"name":"Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp070477"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/499406"},{"key":"e_1_3_2_4_2","volume-title":"Antibiotic resistance threats in the United States, 2013","author":"Centers for Disease Control and Prevention","year":"2013","unstructured":"Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States, 2013. Centers for Disease Control and Prevention, Atlanta, GA. http:\/\/www.cdc.gov\/drugresistance\/threat-report-2013\/pdf\/ar-threats-2013-508.pdf."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2013.03.032"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp197"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00756-10"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01722-10"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01198-10"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00851-12"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01696-10"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.06064-11"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1179\/1973947813Y.0000000145"},{"key":"e_1_3_2_14_2","volume-title":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard","author":"Clinical Laboratory Standards Institute","year":"2011","unstructured":"Clinical Laboratory Standards Institute. 2011. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 8th ed. CLSI publication M07-A8. 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